Overview
Definition:
Galactosemia is an autosomal recessive metabolic disorder characterized by the body's inability to properly metabolize galactose, a sugar found in milk
This leads to the accumulation of toxic galactose metabolites, primarily galactose-1-phosphate, in various tissues.
Epidemiology:
Classic galactosemia occurs in approximately 1 in 30,000 to 60,000 live births, depending on the population
Non-classic forms exist with varying prevalence
Newborn screening programs have significantly reduced the incidence of severe complications.
Clinical Significance:
Untreated galactosemia can lead to severe, life-threatening complications including liver failure, sepsis, cataracts, and intellectual disability
Early diagnosis and strict dietary management are crucial for optimal outcomes and preventing long-term sequelae, especially in female patients.
Clinical Presentation
Symptoms:
Vomiting and diarrhea
Poor feeding and failure to thrive
Jaundice
Lethargy and irritability
Hepatomegaly and ascites
Cataracts (cloudy lenses)
Urinary tract infections (especially E
coli sepsis in infants)
Seizures
Hypotonia.
Signs:
Hepatomegaly
Splenomegaly
Jaundice
Edema
Signs of dehydration or malnutrition
Clouding of the lens on eye examination
Signs of sepsis.
Diagnostic Criteria:
Diagnosis is suspected in infants presenting with the above symptoms, especially after milk feeding, and confirmed by laboratory testing
Newborn screening programs detect elevated galactose or its metabolites
Definitive diagnosis requires enzyme assay for galactose-1-phosphate uridyltransferase (GALT) activity.
Diagnostic Approach
History Taking:
Detailed feeding history (especially intake of milk or dairy products)
Onset of symptoms
Family history of similar conditions or unexplained infant deaths
Prenatal history
History of jaundice or infections in the newborn period
Red flags: rapid deterioration following milk feeds.
Physical Examination:
Assess for jaundice, hepatomegaly, splenomegaly, ascites, and edema
Evaluate hydration status and nutritional markers
Perform a thorough neurological examination
Examine the eyes for cataracts.
Investigations:
Newborn screening: GALT enzyme activity assay or direct measurement of galactose-1-phosphate
Urine screening: Detecting reducing substances (e.g., galactose, glucose) and specific metabolites (e.g., galactitol)
Blood tests: Liver function tests (LFTs), complete blood count (CBC), coagulation profile, blood glucose, ammonia
Genetic testing for specific mutations in GALT, GALK1, or GALE genes may be performed for confirmation and carrier testing.
Differential Diagnosis:
Galactosemia must be differentiated from other causes of neonatal cholestasis, hypoglycemia, failure to thrive, and sepsis
These include other inborn errors of metabolism, congenital infections (e.g., TORCH), biliary atresia, neonatal hepatitis, and sepsis due to other pathogens.
Management
Initial Management:
Immediate cessation of lactose-containing feeds (breast milk and standard infant formulas)
Initiation of a galactose-free diet using soy-based or protein hydrolysate formulas
Supportive care including fluid and electrolyte management, treatment of sepsis, and management of liver failure or hypoglycemia.
Dietary Management:
Strict, lifelong galactose-free diet is the cornerstone of management
This involves avoiding all milk and dairy products, as well as foods containing lactose or galactose
Special formulas (e.g., soy-based, protein hydrolysate) are used for infants
As children age, careful attention is needed to avoid hidden sources of galactose in processed foods, medications, and supplements
Regular monitoring of growth, nutritional status, and biochemical markers is essential.
Surgical Management:
Not applicable for the primary treatment of galactosemia
Surgical interventions may be required for complications such as liver transplantation in cases of end-stage liver disease, or ophthalmological procedures for cataracts.
Supportive Care:
Regular monitoring of growth and development
Nutritional assessment and supplementation as needed
Management of chronic complications like cognitive deficits
Psychosocial support for the child and family
Close follow-up with a metabolic specialist and multidisciplinary team.
Complications
Early Complications:
Sepsis (especially E
coli)
Liver failure (hepatomegaly, coagulopathy, hypoglycemia, ascites)
Renal tubular dysfunction
Cataracts
Hemolytic anemia.
Late Complications:
Developmental delays and intellectual disability
Speech and language deficits
Ovarian failure in females (hypergonadotropic hypogonadism)
Neurological issues (e.g., ataxia, tremors)
Osteoporosis
Premature cataracts.
Prevention Strategies:
Early diagnosis through newborn screening and prompt initiation of a galactose-free diet are paramount
Lifelong adherence to the diet is critical to prevent both early and late complications
Regular ophthalmological and developmental assessments are key to early detection and management of sequelae.
Ovarian Failure Surveillance
Definition:
Premature ovarian failure (POF) or hypergonadotropic hypogonadism is a frequent long-term complication in females with classic galactosemia, often occurring in late adolescence or early adulthood
It is characterized by the cessation of menstruation and infertility due to depletion of ovarian follicles.
Risk Factors:
Genetic factors and the severity of galactose exposure during early infancy are thought to contribute
The exact mechanism is not fully understood but likely involves toxic effects of galactose metabolites on ovarian follicles.
Surveillance Strategy:
Regular monitoring of menstrual cycles starting in early adolescence
Measurement of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels if menstrual irregularities are noted
Ovarian ultrasound may be used to assess ovarian morphology and follicle count
Genetic counseling regarding fertility is important.
Management Of Ovarian Failure:
Hormone replacement therapy (HRT) can be initiated to manage menopausal symptoms and protect bone health
Fertility options such as oocyte donation and in vitro fertilization (IVF) may be discussed, though success rates can be variable
Psychosocial support is crucial for patients dealing with infertility.
Key Points
Exam Focus:
The critical importance of a galactose-free diet is paramount
Recognize E
coli sepsis as a common early complication
Understand the high incidence of premature ovarian failure in female patients
Newborn screening is a vital diagnostic tool.
Clinical Pearls:
Always consider galactosemia in a neonate with unexplained sepsis, vomiting, jaundice, and hepatomegaly, especially after milk feeding
Emphasize strict dietary adherence to patients and families, including hidden galactose sources
Educate about the long-term risk of ovarian failure in females early in adolescence.
Common Mistakes:
Delaying diagnosis by not suspecting galactosemia in symptomatic infants
Inadequate dietary counseling leading to intermittent galactose exposure
Failing to screen for or manage premature ovarian failure in adolescent females
Overlooking E
coli sepsis as a primary complication.