Rare Infectious Disease News

Disease Profile

Hypermethioninemia due to S-adenosylhomocysteine hydrolase deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Psychomotor delay due to S-adenosylhomocysteine hydrolase deficiency; Psychomotor retardation due to S-adenosylhomocysteine hydrolase deficiency; Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Hypermethioninemia due to S-adenosylhomocysteine hydrolase deficiency (SAHH deficiency) is a muscle disease associated with high blood levels of methionine and creatine kinase (CK). The main symptoms are psychomotor delay, behavioral disorders, severe myopathy, and delayed myelination from birth. Myelin is the layer covering the axons of nerves and plays an important role in nerve impulse conductionSAHH deficiency is caused by mutations in the AHCY gene. Inheritance is autosomal recessive.[1][2] A methionine-restricted diet, together with creatine supplements, may partly improve the delayed myelination and psychomotor development. The outcome depends upon the severity of the disease.[2]

Symptoms

Very few patients have being reported with this disease. SAHH patients may not have any symptoms. The observed signs and symptoms in the reported patients included:[1][2]

  • Muscle disease (myopathy) with a blood exam showing an increase of the CK activity (in 100% of the reported cases)
  • Hypotonia
  • Developmental delay
  • Behavioral disorders
  • Very small head (microcephaly)
  • Myelination delay
  • Strabismus
  • Problems with blood coagulation
  • Liver disease

Two sisters had fetal hydrops, brain anomalies and respiratory failure and death in early infancy. Also, a recent report described a 29 year old woman who had liver cancer.[2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Elevated hepatic transaminase
High liver enzymes
0002910
Hyperhomocystinemia
Elevated blood homocystine
0002160
Hypoalbuminemia
Low blood albumin
0003073
30%-79% of people have these symptoms
Abnormal facial shape
Unusual facial appearance
0001999
Cerebellar hypoplasia
Small cerebellum
Underdeveloped cerebellum

[ more ]

0001321
CNS hypomyelination
0003429
Delayed myelination
0012448
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Elevated coagulation factor V activity
0011996
Elevated serum creatine kinase
Elevated blood creatine phosphokinase
Elevated circulating creatine phosphokinase
Elevated creatine kinase
Elevated serum CPK
Elevated serum creatine phosphokinase
High serum creatine kinase
Increased CPK
Increased creatine kinase
Increased creatine phosphokinase
Increased serum CK
Increased serum creatine kinase
Increased serum creatine phosphokinase

[ more ]

0003236
Esotropia
Inward turning cross eyed
0000565
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Global developmental delay
0001263
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth

[ more ]

0001510
Hydrops fetalis
0001789
Hyperintensity of cerebral white matter on MRI
0030890
Hypofibrinogenemia
0011900
Hypoplasia of the corpus callosum
Underdevelopment of part of brain called corpus callosum
0002079
Hypoplasia of the pons
0012110
Infantile muscular hypotonia
Decreased muscle tone in infant
0008947
Muscular dystrophy
0003560
Poor head control
0002421
Prolonged prothrombin time
0008151
Reduced antithrombin III activity
0001976
Reduced factor VII activity
0008169
Short attention span
Poor attention span
Problem paying attention

[ more ]

0000736
5%-29% of people have these symptoms
Abnormality of hair texture
0010719
Abnormality of the dentition
Abnormal dentition
Abnormal teeth
Dental abnormality

[ more ]

0000164
Cardiomyopathy
Disease of the heart muscle
0001638
Hepatocellular carcinoma
0001402
Hypermethioninemia
Increased methionine in blood
0003235
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Pes planus
Flat feet
Flat foot

[ more ]

0001763
Respiratory failure
0002878
Sensorimotor neuropathy
Nerve damage causing decreased feeling and movement
0007141
Ventriculomegaly
0002119
Widened subarachnoid space
0012704
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Motor delay
0001270

Treatment

Because this disease affects many organs and may begin before birth, it may be difficult to treat. It is possible that blood abnormalities are present in all patients in utero.[1]

Treatment may include:[2]

  • A low methionine diet: This can decrease and sometimes even normalize the abnormalities in the blood exams. Patients have to be on a protein restricted diet and supplemented with a methionine-free amino acid mixture.
  • Supplementation with phosphatidylcholine and creatine: At this time there is no evidence that this treatment is effective.
  • Liver transplantation: Recently, liver transplantation was successfully done in one girl at the age of 40 months, but longer follow-up is needed to know the outcome of the liver transplantation.

The treatment outcome depends on the severity of the disease. It is not known whether even early intervention could help in severe cases. In others, it is possible that earlier initiation of treatment may improve the outcome. Regular careful evaluation of all body systems is indicated, mainly of the nervous system, psychomotor development, muscles, liver and blood (for coagulation). This includes imaging studies, especially regular liver imaging and blood exams.[2]

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

References

  1. Hypermethioninemia. Genetics Home Reference:. April, 2007; https://ghr.nlm.nih.gov/condition/hypermethioninemia.
  2. Baric I. Consensus recommendations for the diagnosis, treatment and follow-up of inherited methylation disorders. J Inherit Metab Dis. September 26, 2016; https://www.ncbi.nlm.nih.gov/pubmed/27671891.

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