HSD10 disease (Alpha Methyacetoacetic Aciduria)

What is HSD10 disease (Alpha Methyacetoacetic Aciduria)

HSD10 disease is a rare, life-threatening neurometabolic disease characterized by a progressive neurodegenerative course, epilepsy, retinopathy and progressive cardiomyopathy.

This condition is also known as the Alpha Methyacetoacetic Aciduria


2-methyl-3-Hydroxybutyric Acidemia
Beta-Kethothiolase Deficiency
Mitochondrial Acetoacetyl-CoA Thiolase Deficiency
Mat Deficiency
T2 Deficiency
3-Oxothiolase Deficiency
3-Kethothiolase Deficiency

MHBD deficiency
3-KTD Deficiency

Prevalence of HSD10 disease

<1 / 1000000


40 cases have been reported worldwide

Age of onset

  1. Childhood
  2. Infancy
  3. Neonatal

Symptoms of HSD10 disease

Very common symptoms

  • Abnormal urinary acylglycine profile 

common symptoms

  • Delayed speech and language development 
  • Developmental regression 
  • Elevated urinary 3-hydroxybutyric acid 
  • Global developmental delay 
  • Intellectual disability, moderate 
  • Progressive visual loss 
  • Seizures 
  • Specific learning disability 

Occasional Symptoms

  • Abnormal social behavior 
  • Ataxia 
  • Autistic behavior 
  • Behavioral abnormality 
  • Choreoathetosis 
  • Chronic lactic acidosis 
  • Dysarthria 
  • Focal white matter lesions 
  • Frontotemporal cerebral atrophy 
  • Gait disturbance 
  • Hearing impairment 
  • Infantile muscular hypotonia 
  • Myoclonus 
  • Optic atrophy 
  • Short attention span 

Rare Symptoms

  • Drooling 
  • Dysphagia 
  • Gastrointestinal dysmotility 
  • Hyperreflexia 
  • Microcephaly
  • Nasogastric tube feeding in infancy 
  • Nonprogressive encephalopathy 
  • Nystagmus 
  • Postnatal growth retardation 
  • Rigidity 
  • Spastic paraparesis 
  • Tremor 
  • Ventriculomegaly 

Prognosis of HSD10 disease

The prognosis is poor, especially for the neonatal and infantile forms of the disease.

The prognosis for the attenuated or asymptomatic variants of the disease is currently unknown.

Treatment of HSD10 disease

  1. At present, there is no effective treatment for the disease.
  2. A low-protein, high-energy dietary regimen with carnitine supplementation reduces the accumulation of isoleucine metabolites in blood and urine, but does not improve psychomotor deterioration.
  3. Due to its ability to interfere with mitochondrial energy metabolism, valproic acid should be avoided.