Medical management of Genetic Disorders

This page lists important national and international protocols for the treatment of genetic diseases as a reference for consultation. All references listed are intended for healthcare professionals who deal with patients with genetic disorders. Because these are very rare conditions, and it is difficult to generate new evidence, some approaches may differ between different authors. Emergency guidelines and drug databases should be used with caution, following the terms of use described by the authors on their website.

2-methylbutyryl-CoA dehydrogenase deficiency

DDIEM - IEM drug database

22q11.2 deletion syndrome

Genereviews  - Review on diagnosis and management

3-hydroxy-3-methylglutaryl-CoA lyase deficiency

New England Consortium- Emergency Treatment

DDIEM - Drug database

Grunert & Sass, 2020 - Review of all published cases, with discussion of treatments

OMMBID -Review of diagnosis and treatment of ketogenesis disorders

3-methyl-crotonyl-CoA carboxylase deficiency - 3MCC

New England Consortium of Metabolic Programs - emergency treatment

Arnold et al., 2008 - International consensus on diagnosis and management

AADC deficiency

Wassenberg, 2017 - Diagnosis and treatment consensus.

DDIEM - IEM drug database

Achondroplasia

Poskanzer SA et al., 2023 - ACMG guidelines on vosoritide treatment.

Acid Sphingomyelinase Deficiency - ASMD (Niemann-Pick A, Niemann Pick A/B and Niemann-Pick B)

Geberhiwot et al., 2023 - International consensus clinical management guidelines

Genereviews - Point-of-care review on diagnosis and treatment of ASMD

ADCY5, discinesia

Genereviews  - Revisão de diagnóstico e tratamento.

Aicardi-Goutières syndrome

Gedik et al., 2022 - Consensus on diagnosis and treatment of Aicardi-Goutières syndrome

Vanderver et al., 2020 - Open-label study of baricitinib on Aicardi-Goutières syndrome. Includes detailed information on dosis, safety and efficacy evaluations in the supplementary material.

 

Argininosuccinate lyase deficiency (argininosuccinic aciduria)

Genereviews -  review

Baruteau et al., 2019 - Review on pathophysiology and therapeutic perspectives

Frez et al., 2011 - Review on pathophysiology, diagnosis and treatment

New England Consortium of Metabolic Programs - emergency treatment

E-IMD  

BAP1 tumour predisposition syndrome

Lalloo et al., 2023 - Clinical practice guidelines for the diagnosis and surveillance

Beta-ketothiolase deficiency

Grünert & Sass, 2020 - Review of all published cases, with discussion of treatments

Biotinidase deficiency

Tankeu et al., 2023 - Review of published case series, including sign and symptoms, clinical presentation, outcomes. 

Wolf, 2022 - Commentary about use of biotin in biotin-responsive disorders.

PCDT, 2018 - Brazilian Public Health system guidelines

Wolf, 2012 - Comprehensive review of practical issues on the diagnosis and management of Biotinidase deficiency

Genereviews 

Cerebrotendinous Xanthomatosis

DDIEM - Dadabase of medications for IEM

Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature - CANDLE / PRAAS

Sanchez et al., 2018 - Study on the use of baricitinib in patients with CANDLE and other interpheronopathies.

Citrullinemia type I

Genereviews - Practical review of diagnosis and treatment.

Yuan et al., 2021 - Evaluation of liver transplant outcomes in a single center

E-IMD

Deficiency of Adenosine Deaminase 2 - DADA2

Lee et al., 2023 - International Consensus Statement

Genereviews  - review

 

Diamond-Blackfan anemia

Da Costa et al., 2020 - Comprehensive review

Fabry disease

Genereviews

Stepien et al., 2023 - UK consensus

Burlina et al., 2023 - Biomarkers for Fabry Disease

Wanner et al., 2018 - European consensus on therapeutic goals

Ortiz et al., 2018 - Expert consensus on management of adult patients

Germain et al., 2019 - Expert consensus on management of children

Diretrizes Brasileiras - Brazilian public health system guidelines for diagnosis and treatment of Fabry disease

Généo, 2021 - Treatment protocol of the French Fabry Disease Reference Center.

Sirrs et al., 2018 - Canadian Protocol

Australian Government - Australian government criteria for initiation and renewal of treatment with agalsidase alfa, agalsidase beta and migalastat.

 

Familial Adenomatous Polyposis (FAP)

NCCN - cancer prophylaxis recommendations.

Free sialic acid storage disease

Genereviews - General review of diagnosis and treatment of free sialic acid storage disease

Galactosemia II (GALK deficiency)

Rubio-Gozalbo et al., 2021 - Clinical description of 53 patients

Gaucher disease

PCDT Gaucher 2017 - Brazilian Government treatment guidelines.

Kishnani PS et al., 2021 - International Delphi consensus on diagnosis and treatment

Biegstraaten M et al., 2018 - Therapeutic goals in Gaucher disease

GLUT1 deficiency

Keppler et al., 2020 - Recommendations from the International Glut1 Deficiency Study Group

Tang et al., 2019 - Discusses therapeutic strategies applied to Glut1 deficiency

Glutaric aciduria type 1

BIMDG -Emergency Treatment

Boy et al., 2022 - Revised international guidelines on the treatment of type I glutaric aciduria.

Strauss et al., 2020 - It describes the glutaric acidemia treatment strategy used at the Clinic for Special Children in Pennsylvania and discusses aspects of diagnosis and prognosis.

E-IMD - Summary booklet for health professionals on type I glutaric aciduria.

Genereviews - General review on diagnosis and treatment.

Glycogen Storage Disease type IV and Adult Polyglucosan Body Disease

Koch et al., 2023 - Guidelines from the Association for Glycogen Storage Disease (AGSD) in the United States

Genereviews - review

 

Glycogen Storage Disease Type V and VII (McArdle and Tarui diseases)

Lucia et al., 2021 - Treatment guidelines, including guidance on monitoring in supplementary article material.

 

Hereditary breast and ovarian cancer syndrome - HBOC

NCCN - recommendations for cancer prevention.

Homocystinuria, Classic

PCDT, 2020 - Brazilian Public Healthcare System clinical protocols and therapeutic guidelines

Morris et al., 2016

Isolated methylmalonic acidemia (MUT, CblA, CblB, CblD-MMA)

Forny et al., 2021 - European guideline of methylmalonic and propionic acidemia. Includes acute management and long-term follow-up. Review of the original 2014 protocol

Genereviews  - Review of diagnosis and treatment

E-IMD 

Isovaleric Acidemia

BIMDG - Emergency treatment

New England Consortium - Emergency treatment

E-IMD - Concise review on diagnostic principles, treatment and prognosis

Manoli & Venditti, 2016 - Discusses branched-chain (including isovaleric) organic acidurias

Vockley, 2006 - Review on isovaleric acidemia

DDIEM - Lists drugs used in isovaleric acidemia and respective references that support their use.

Ketogenic Diet

van der Louw et al, 2016 - Treatment guidelines in infants

Kossoff et al., 2018 - clinical management guidelines from the International Ketogenic Diet Study Group

Lesch-Nyhan Syndrome

Genereviews - review on diagnosis and treatment

Li-Fraumeni Syndrome

Kratz et al., 2017 - Screening recommendations

Liver transplant for metabolic disorders

Oishi et al., 2016 - Overview of liver transplantation in IEM

Lynch Syndrome

NCCN - cancer prophylaxis recommendations.

Seppäla et al, 2021 - European gene and gender-specific management guidelines

Maple syrup urine disease - MSUD

Rodan et al., 2018 - Emergency treatment, from the Boston Children's Hospital group.

New England Consortium of Metabolic Programs - Emergency Treatment

Southeast Regional Genetics Network / GMDI - Nutritional management guidelines

Strauss et al., 2020 - Clinic for Special Children Guidelines (Strasburg, PA, USA)

 

Medium chain acyl-CoA dehydrogenase deficiency (MCAD)

Genereviews - Review on diagnosis and treatment

New England Consortium - Emergency guidelines

Methylenetetrahydrofolate reductase (MTHFR) deficiency

Huemer et al., 2016  - E-HOD Guidelines . Includes other remethylation disorders.

Mitochondrial diseases

Tinker et al., 2021 - Review of treatments currently available and under development

Barcelos et al., 2020 - Evidence-based review of therapies for mitochondrial diseases

Parick et al., 2017 - Consensus on the care of patients with primary mitochondrial diseases

Parick et al., 2014 - Consensus on diagnosis and management

Mitochondrial Neurogastrointestinal Encephalopathy - MNGIE

Hirano et al., 2020 - Article elaborated after an international consensus conference, describing diagnosis, prognosis and treatment.

Filosto et al., 2018 - General review

MPI‐CDG

Čechová A., et al., 2020 - Guidelines

Mucopolysaccharidosis type I - MPS I

Kubaski et al., 2020 - Review on diagnosis and treatment

PCDT, 2018 -Brazilian Public Health System Guidelines

Mucopolysaccharidosis type II

McBride et al., 2020 - ACMG recommendations

PCDT 2018 - Brazilian Public Health System Guidelines

Mucopolysaccharidosis type III

Muschol et al. 2022 - Clinical management consensus

Mucopolysaccharidosis type IVA

Akyol et al., 2019 - International Consensus

PCDT 2020 - Brazilian Public Health System Guidelines

Mucopolysaccharidosis type VI

Akyol et al., 2019 - International Consensus of Experts

PCDT 2020 - Brazilian Public Health System Guidelines

Multiple Endocrine Neoplasia types 2A and 2B (MEN2A and MEN2B)

Genereviews - Practical review of diagnosis and management.

Wells Jr, 2015 - American Thyroid Association Management Guidelines for Medullary Thyroid Carcinoma, including MEN2A and MEN2B

Neuronal ceroid lipofuscinosis 1 (CLN1)

Augustine et al., 2021 - International Clinical Consensus

Neuronal Ceroid Lipofuscinosis Type 2 (CLN2)

Guelbert et al., 2020 - Review by Latin American experts with recommendations for clinical follow-up

NGLY1-CDDG

Genereviews - A review on NGLY1-Related Congenital Disorder of Deglycosylation

Nonketotic hyperglycinemia

Genereviews - Review on diagnosis and treatment

Nowak et at., 2022 - review of available treatments.

Hennerman et al., 2011 - Prognosis of patients with NKH

 

PALB2 germline variants

Tischkowitz, 2021 - ACMG recommendations for management of individuals with PALB2 variants

Peutz-Jeghers Syndrome

NCCN - recommendations for cancer prevention

PGM1-CDG

Altassan R et al., 2021 - Diagnosis and treatment guidelines

PMM2-CDG

Genereviews - Diagnosis and treatment guidelines

Altassan et al., 2019 - International diagnosis and treatment guidelines

Pompe disease

PCDT, 2020 - Brazilian Public Health System Guidelines

Kishnani, 2006 - ACMG recommendations for diagnosis and management

Porphyria Cutanea Tarda

Genereviews

DDIEM - IEM drug database

Porphyria, Acute Intermittent - AIP

Genereviews

Anderson KE, 2019 - Diagnosis and treatment of acute hepatic porphyrias

Stölzel et al., 2019 - Clinical Guide and Update on Porphyrias, including short case reports

Karim et al., 2015

DDIEM - IEM drug database

Porphyria, Variegate

Genereviews

Stölzel et al., 2019 - Clinical Guide and Update on Porphyrias, including short case reports

Anderson KE, 2019 - Diagnosis and treatment of acute hepatic porphyrias

Karim et al., 2015 - General review on porphyrias, including very useful figures and tables.

Prolidase Deficiency

Genereviews - review

Spodenkiewicz et al., 2020 - general review.

Propionic Acidemia

Forny et al., 2021 - European guideline of methylmalonic and propionic acidemia. Includes acute management and long-term follow-up. Review of the original 2014 protocol

Jurecki et al., 2019 - Consensus and evidence-based review on nutritional management.

Genereviews - review

British Inherited Metabolic Group (BIMDG) - Emergency treatment

New England Consortium of Metabolic Programs - Emergency treatment

Southeast Regional Genetics Network / GMDI - Emergency treatment

Protoporphyria, X-linked

Genereviews - review on diagnosis and treatment

Pyridoxine dependent epilepsy - PDE

Coughlin et al., 2020 - consensus on the diagnosis and management of pyridoxine-dependent epilepsy due to alpha-aminoadipic semialdehyde dehydrogenase deficiency

Retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and headache (ROSAH)

Kozycki et al., 2022 - Phenotypic description and report of clinical response to tocilizumab

SLC35A2-CDG

Yates et al., 2018 - Case series with comprehensive description of the clinical phenotype

Sosicka et al., 2019 - Review of 30 cases with an analysis of prevalence of manifestations

Witters et al., 2020 - Galactose supplementation

 

Smith-Lemli-Opitz Syndrome (SLOS)

Genereviews

Ballout et al., 2022 - Cochrane review on Statins for Smith-Lemli-Opitz syndrome

Svoboda et al., 2012 - Treatment of Smith-Lemli-Opitz syndrome and other sterol disorders

Porter, 2008 - Pathogenesis, diagnosis and management

Spinal Muscular Atrophy

PCDT, 2022 - Brazilian Public Health System Guidelines

Cartwright, 2021 - Review on the therapeutic options - nusinersen, onasemnogene abeparvovec and risdiplam

Tetrahydrobiopterin (BH4) deficiency

Opladen et al., 2020 - International Working Group on Neurotransmitter Related Disorders (iNTD) Consensus Guideline

Urea Cycle Disorders

Häberle et al., 2019 - Review on diagnosis and treatment, including symptomatic management (2012 guideline update)

Very Long Chain Acyl-CoA Dehydrogenase Deficiency (VLCAD)

Southeast Regional Genetics Network / GMDI

Calcad et al., 2020 - Consensus and evidence-based review on nutritional management

Genereviews - Review of diagnosis and treatment.

New England Consortium- Emergency Treatment

von Hippel Lindau disease

Daniels et al., 2023 - Guidelines for surveillance

Wilson Disease

PCDT, 2018 - Brazilian Public Health System Guidelines

Zellweger spectrum disorders

Braverman et al., 2016 - Review on diagnosis and treatment, including symptomatic management

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