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.